6631-94-3

Usage

Uses

Used in Anticancer Applications:
2-Acetylphenothiazine is used as an inhibitor for NOX1-dependent ROS generation in human DLD1 colon cancer cells, preventing the formation of ECM-degrading invadopodia and potentially contributing to the development of novel cancer treatments.
Used in Platelet Functional Responses and Signaling Pathways:
2-Acetylphenothiazine is used as a NADPH oxidase (NOX) inhibitor in human platelet functional responses and intracellular signaling pathways, with the ability to abolish collagen-induced superoxide production by platelets, thus preventing platelet aggregation and thrombus formation.
Used in Synthesis of Derivatives:
2-Acetylphenothiazine is utilized in the synthesis of 2-phenothiazin-2′-yl-cinchoninic acid derivatives, which may have various applications in the pharmaceutical and chemical industries.
Used in Beta Cell Protection:
2-Acetylphenothiazine is used as a protective agent for beta cells, inhibiting NOX1 and thus protecting them from cytokine-induced apoptosis, which could be beneficial in the treatment of diabetes.
Used in Activation of TRPA1 Nociceptor:
2-Acetylphenothiazine is used as an activator for the human transient receptor potential ankyrin 1 (TRPA1) nociceptor at concentrations between 1-30 μM, which may have implications in the study and treatment of pain and sensory perception.

InChI:InChI=1/C14H11NOS/c1-9(16)10-6-7-14-12(8-10)15-11-4-2-3-5-13(11)17-14/h2-8,15H,1H3

Upstream product

• 1628-29-1 10-acetyl-10H-phenothiazine 
• 75-36-5 acetyl chloride 
• 6632-11-7 1-(2-acetyl-10H-phenothiazin-10-yl)ethan-1-one 
• 80838-42-2 2-acetyl-10-(chloroacetyl)-10H-phenothiazine 
• 506-96-7 Acetyl bromide 
• 108-24-7 acetic anhydride 
• 23699-65-2 1-(3-(phenylamino)phenyl)ethan-1-one 
• 103-70-8 Formanilid 
• 99-02-5 3'-Chloroacetophenone 
• 18956-87-1 10H-phenothiazine-10-carbonyl chloride 
• 92-84-2 10H-phenothiazine 
• 94708-81-3 2-acetyl-10-(3-chloro-propionyl)-10H-phenothiazine 
• 29957-73-1 phosphoric acid 1-(10-acetyl-10H-phenothiazin-2-yl)-vinyl ester diethyl ester 
• 74240-96-3 2-acetyl-phenothiazine-10-carbonyl chloride 

Downstream Products

• 89516-42-7 2-(β-pyrrolidinopropanoyl)phenothiazine 
• 89516-40-5 2-(β-hexamethyleniminopropanoyl)phenothiazine 
• 89516-44-9 2-<β-4-(o-methoxyphenylphenyl)piperazinopropanoyl>phenothiazine 
• 120492-16-2 1-(10H-phenothiazine-2-yl)-3-(4-methylphenyl)prop-2-en-1-one 
• 120492-17-3 1-(10H-phenothiazine-2-yl)-3-(4-chlorophenyl)prop-2-en-1-one 
• 81102-97-8 1-(10H-phenothiazine-2-yl)-3-phenylprop-2-en-1-one 
• 81102-98-9 3-(4-methoxyphenyl)-1-(10H-phenothiazin-8-yl)prop-2-en-1-one 
• 61-00-7 acetopromazine 
• 63285-55-2 2-(3-Pyrazolyl)phenothiazin 

Relevant academic research and scientific papers

Method for synthesizing 2-acetyl phenothiazine using phenothiazine as raw material

The present invention discloses a method for synthesizing 2-acetyl phenothiazine using phenothiazine as a raw material. The method comprises: by using silicon dioxide as a catalyst, heating phenothiazine with formic acid by microwave radiation for a nucleophilic substitution reaction; conducting an electrophilic substitution reaction on the product obtained in the first step and acetyl chloride under catalysis of aluminium trichloride in a dimethyl sulphone solvent; and conducting a hydrolysis reaction on the product obtained in the second step under catalysis of a strong base. According to the method provided by the invention, phenothiazine is used as the raw material, and through N-formylated nucleophilic substitution, electrophilic substitution on benzene rings and hydrolysis of N-acylamino, 2-acetyl phenothiazine is obtained. According to the method disclosed by the invention, secondary amine is formylated in the method to weaken the positioning effect of N atoms on phenyl rings in ortho-position and para-position of the N atoms, so that the leading role of S atoms on the positioning effect in the ortho-position and the para-position of the S atoms s ensured, and the yield of a target product 2-position acetyl substituted product is significantly improved, thereby ensuring the total yield and purity of 2-acetyl phenothiazine.

Method for synthesis of 2-acetylphenothiazine from m-acetylchlorobenzene and benzamide

The invention discloses a method for synthesis of 2-acetylphenothiazine from m-acetylchlorobenzene and benzamide. The method comprises that m-acetylchlorobenzene and benzamide undergo a Ullmann condensation reaction in a tert-butyl alcohol solvent in the presence of cuprous iodide and piperazine as catalysts, the reaction product undergoes a hydrolysis reaction in the presence of a strong base as a catalyst and the hydrolysis reaction product and a sulfur elementary substance undergo an annulation reaction in an acetone solvent in the presence of iodine as a catalyst. The 2-acetylphenothiazine is prepared from m-acetylchlorobenzene and benzamide as raw materials through a Ullmann condensation reaction, a hydrolysis reaction and an annulation reaction with the sulfur elementary substance. Benzamide is used as a nucleophilic reagent and P electrons on carbonyl carbon of benzamide produce electron donating conjugative effects so that electron cloud density of aryl nitrogen atoms is increased, nitrogen atom nucleophilicity is improved and a Ullmann condensation reaction rate is accelerated. The method guarantees a 2-acetylphenothiazine overall yield and purity through above two steps.

Method for synthesis of 2-acetyl phenothiazine with m-acetyl phenol and aniline as raw materials

The invention discloses to a method for synthesis of 2-acetyl phenothiazine with m-acetyl phenol and aniline as raw materials. The method comprises the steps: carrying out a dehydration reaction of m-acetyl phenol and aniline with trifluoromethanesulfonic acid as a catalyst; and carrying out an annulation reaction on the product obtained in the first step with elemental sulfur under the catalysis of iodine in an acetone solvent. With m-acetyl phenol and aniline as the raw materials, firstly, amino and phenolic hydroxyl are subjected to dehydration reaction, then the product is subjected to annulation reaction with elemental sulfur, and thus 2-acetyl phenothiazine is obtained. Trifluoromethanesulfonic acid as the dehydration reaction catalyst has stronger acidity and has the effect of relatively strongly protonizing m-acetyl phenol to form a molten salt, and the dehydration yield is increased. Through the two steps, the total yield and purity of 2-acetyl phenothiazine are ensured.

Assembly of substituted phenothiazines by a sequentially controlled CuI/L-proline-catalyzed cascade C-S and C-N bond formation

(Chemical equation presented) In the pro-line of fire: A general and efficient cascade reaction approach to substituted phenothiazines, which relies on controlled sequential Cul/L-prolinecatalyzed C-S and C-N bond formations, is described. DMSO = dimethylsulfoxide.

Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs

Given the role of trypanothione in the redox defenses of pathogenic trypanosomal and leishmanial parasites, in contrast to glutathione for their mammalian hosts, selective inhibitors of trypanothione reductase are potential drug leads against trypanosomiasis and leishmaniasis. In the present study, the rational drug design approach was used to discover tricyclic neuroleptic molecular frameworks as lead structures for the development of inhibitors, selective for trypanothione reductase over host glutathione reductase. From a homology-modeled structure for trypanothione reductase, replaced in the later stages of the study by the X-ray coordinates for the enzyme from Crithidia fasciculata, a series of inhibitors based on phenothiazine was designed. These were shown to be reversible inhibitors of trypanothione reductase from Trypanosoma cruzi, linearly competitive with trypanothione as substrate and noncompetitive with NADPH, consistent with ping-pong bi bi kinetics. Analogues, synthesized to define structure-activity relationships for the active site, included N-acylpromazines, 2-substituted phenothiazines, and trisubstituted promazines. Analysis of K(i) and I50 data, on the basis of calculated log P and molar refractivity values, provided evidence of a specially favored fit of small 2-substituents (especially 2-chloro and 2-trifluoromethyl), with a remote hydrophobic patch on the enzyme accessible for larger, hydrophobic 2-substituents. There was also evidence of an additional hydrophobic enzymic region available to suitable N-substituents of the promazine nucleus. K(i) data also indicated that the phenothiazine nucleus can adopt more than one inhibitory orientation in its binding site. Selected compounds were tested for in vitro activity against Trypanosoma brucei, T. cruzi, and Leishmania donovani, with selective activities in the micromolar range being determined for a number of them.

Potential CNS antitumor agents - phenothiazines I: Nitrogen mustard derivatives

Four phenothiazine derivatives containing the bis (β chloroethyl) aminopropyl side chain were prepared and evaluated in the murine L 1210, P 388 and B 16 melanoma intraperitoneal tumor systems. Moderate P 388 activity was observed. An aminoethyl phenothiazine mustard was compared with the aminopropyl analogs and was superior in all test systems. None of the compounds tested against the murine ependymoblastoma brain tumor system was active.